Single-cell analysis reveals transcriptomic difference between keloid and normal human tissue
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE282885 | GEO | 2025/11/11
REPOSITORIES: GEO
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Project description:Background Hypertrophic scars and keloids are both pathological scars with similar appearance and pathological features. Currently, the differential diagnosis of the two mainly depends on the subjective judgment of physicians, and there is a lack of objective diagnostic indicators and treatment methods. Objectives To provide single-cell level evidence and new approaches for the differential diagnosis and clinical treatment of hypertrophic scars and keloids. Methods Single-cell RNA sequencing (scRNA-seq) was performed on a hypertrophic scar and a keloid tissue from the same patient to compare the differences in the cellular and tissue microenvironments of the two conditions. Results ScRNA-seq results depicted the distribution of cell subpopulations and different microenvironments between hypertrophic scars and keloids. Conclusions The results of the analysis showed significant differences in cell subcluster distribution and cell communication between hypertrophic scars and keloids. This study demonstrated the potential of scRNA-seq to differentiate the two conditions and provide a new approach to refine differential diagnosis and a possible target for therapeutic research.
2024-11-15 | GSE243716 | GEO
Project description:Keloid scars is a pathologic fibro-proliferative disorders of the skin, which exhibit abnormal phenotypes including fibroblasts proliferation and collagen deposits. There have been several treatments of keloids including conventional surgical therapies and adjuvant therapies, but a high recurrence rate of keloids was also observed after treatment. Quantitative proteomics approach has been proved an efficient approach to investigate pathological mechanism and novel biomarkers. In this study, we present a label-free quantitative proteomics analysis to explore differential protein expression profiles in normal skin and keloid scar tissues based on nano-liquid chromatography and tandem mass spectrometry (Nano-LC–MS/MS). The study results displayed a more comprehensive keloid protein expression landscape and provided novel pathological insight of keloid.
2023-03-11 | PXD029631 | Pride
Project description:Scars are a heterogeneous disease including normotrophic scars, hypertrophic scars, and keloids. Of these lesions, keloids are a distinct subtype from any other type of scar because clinically, it causes pain, itching, or tenderness, causing life discomfort and characteristically irreversible. Therefore, for accurate diagnosis and treatment of keloids, it is essential to identify keloid-specific genes. However, in previous studies, keloids were compared with controls such as scar-free normal skin. In these studies, general scar-related genes were likely to be chosen rather than keloid-specific genes. In this study, we acquired transcriptomic profiles of normotrophic scars, hypertrophic scars, and keloids from formalin-fixed paraffin-embedded human skin samples using high-throughput RNA-sequencing techniques. We compared the transcriptome profile of keloids with those of other scar lesions to select for highly accurate keloid-specific genes and pathways. The results revealed that genes related with several biological processes such as sensory/visual perception are upregulated strongly in keloids, whereas genes related with activation of immune response were downregulated remarkably in keloids. Furthermore, the biological process of extracellular matrix organization was highlighted in both hypertrophic scars and keloids. In conclusion, our study provides insight into the pathogenesis of keloids distinct from other scar lesions as well as potential keloid-specific biomarkers.
2021-11-23 | GSE188952 | GEO
Project description:We hypothesize that, the mTOR pathway is a dominant pathway in cultured keloid and hypertrophy scar fibriblasts compared to normal skin cells. Certain pathway changes can be detected after medication treatment. Global gene expression in RNA samples from rapamycin and tacrolimus treated fibroblasts (from normal skin and hypertrophic scars, keloid scars) is assayed to study the possibility to use mTOR inhibitors as potential drug to treat abnormal scarring. We investigated the difference between normal wound healing and hypertrophic scars and keloids as well.
2014-05-20 | E-MTAB-2509 | biostudies-arrayexpress
Project description:Keloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes. Skin and scar tissues were obtained for isolation of primary keratinocytes and fibroblasts. Keloid scars were excised from patients undergoing scar excision surgery, normal skin samples were isolated from patients undergoing elective plastic surgery. Primary culters were prepared for keratinocytes and fibroblasts, and were harvested for analysis up to passage three. Nine keloid scars, for adjacent non-lesional keloid skin samples, and three normal skin samples were obtained and cultured. RNA was isolated using RNeasy, and quality verified using an Agilent 2100 Bioanalyzer. Labeling and hybridization to Affymetrix Human Gene 1.0 ST microarray chips was performed by the Vanderbilt Genome Sciences Resource at Vanderbilt University Medical Center.
2013-05-28 | E-GEOD-44270 | biostudies-arrayexpress
Project description:Keloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes.
2013-05-28 | GSE44270 | GEO
Project description:Keloids are benign tumors of the dermis that form during a protracted wound healing process. Susceptibility to keloid formation occurs predominantly in people of African and Asian descent. The key alteration(s) responsible for keloid formation has not been identified and there is no satisfactory treatment for this disorder. The altered regulatory mechanism is limited to dermal wound healing, although several diseases characterized by an exaggerated response to injury are prevalent in individuals of African ancestry. We have observed a complex pattern of phenotypic differences in keloid fibroblasts grown in standard culture medium or induced by hydrocortisone. In this study Affymetrix-based microarray was performed on RNA obtained from fibroblasts cultured from normal scars and keloids grown in the absence and presence of hydrocortisone. We observed differential regulation of approximately 500 genes of the 38,000 represented on the Affymetrix chip. Of particular interest was increased expression of several IGF-binding and IGF-binding related proteins and decreased expression of a subset of Wnt pathway inhibitors and multiple IL-1-inducible genes. Increased expression of CTGF and IGFBP-3 was observed in keloid fibroblasts only in the presence of hydrocortisone. These findings support a role for multiple fibrosis-related pathways in the pathogenesis of keloids Keywords: cell-type comparison, drug treatment comparison Cell cultures were initiated from human biopsy material from normal dermal scars and keloids of adult males and females. Experimental cultures were derived from the first passage of cells thawed from liquid nitrogen. Cultures of fibroblasts from samples were grown with or without 1.5 micromolar hydrocortisone. RNA from each cell strain was isolated from three independent cell cultures and pooled, then run on an Affymetrix Human Genome U133 Plus 2.0 GeneChip.
2007-11-26 | E-GEOD-7890 | biostudies-arrayexpress
Project description:Fibrosis is vaguely described as connective tissue deposition that can be excessive in pathological conditions. This suggests a quantitative spectrum of fibrosis wherein there can be more or less extracellular matrix (ECM), which in the context of a repairing skin wound could reflect the range from normal scar to keloid. This depiction, however, does not encompass the potential qualitative differences between normal and pathological scars. In keloids, the markedly different physical (hard and dense) and histological (hyalinization) characteristics compared to normal scars indicate an altered and inappropriate matrix, rather than simply too much. With this quantitative discovery-based proteomics we provide a thorough molecular description of keloid lesions relative to normal scars, which is an essential step towards our understanding of this problem.
2019-12-03 | PXD015057 | Pride
Project description:Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). The objective was to evaluate the enrichment of myofibroblasts in these tissues. Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Comparison of the results with publicly available RNA-sequencing datasets revealed that 112 genes were significantly upregulated and 108 genes were downregulated in keloid samples compared with immature scar samples. Among them, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. There are two main isoforms of KANK4 transcripts, with short isoforms being dominantly expressed in keloid tissue. Overexpression of the short isoform of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.
2024-03-19 | GSE245660 | GEO
Project description:Keloids are pathological fibroproliferative scars resulting from abnormal collagen deposition within and beyond the margins of the initial cutaneous insult. Keloids negatively impact quality of life cosmetically and functionally and have unsatisfactory treatment modalities with adverse side effects and high reoccurrence rates. Recent studies indicate that epigenetic dysregulation is involved in the development and progression of keloids, suggesting that this could be a viable therapeutic target. The purpose of this study was to evaluate epigenetic targeting drugs, HDACi, LSD1i, Corin, and A-485, as potential therapies for keloids using in-vitro model systems with patient-derived keloid fibroblasts. Results demonstrated that both dual-acting CoREST inhibitor, corin, and HDAC inhibitor, MS-275, reduced fibroblast proliferation more than the LSD1 inhibitor. Corin was the most effective inhibitor of keloid fibroblast migration and invasion across keloid cell lines and primary cells. RNA-seq analysis showed that corin treatment upregulated a significant number of genes with an enrichment in neural differentiation and cell adhesion gene sets. Specifically, corin increased the expression of claudins, which may cause increased cell adhesion and contribute to corin-induced reductions in migration and invasion. Corin downregulated gene sets involved in cell cycle progression, confirmed by reductions in Cyclin A1 and Cyclin B2 at the protein level compared to DMSO. These results highlight the significant role for epigenetic regulation in pathogenic keloid fibroblasts properties and indicate that the epigenetic inhibitor corin may be useful in the prevention and/or treatment of keloids.
2024-07-23 | GSE232079 | GEO